Vorinostat (MK-0683)

A phase II study of Vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia 

Results of the research 

This study, known as the ‘Vorinostat’ trial, was carried out in the UK and Denmark with support from MPN Voice. This support was crucial in getting the trial open and running in the UK.

The trial was an open label study where Vorinostat was given to 63 patients with polycythaemia vera and essential thrombocythaemia in 15 different centres. The primary objective of the trial was to evaluate if Vorinostat treatment lead to a decline in clonal proliferation, in other words, if Vorinostat controlled the blood counts in the patients. The intervention period when the patients were given the drug was 24 weeks. 48% of patients completed the intervention period on drug. 35% of patients had a response in that their blood counts were controlled. Itch also resolved in the 19% of patients who complained of this at the time of entry to the trial.

However, 52% of patients did not complete the 24 week intervention period because of adverse events or lack of response. Consequently, the drug at the dose administered was hard to tolerate.

Samples from the patients were also studied before and after treatment to look at the levels of YKL-40, a growth factor which induces tumour proliferation. There was a significantly greater reduction in YKL-40 in polycythaemia vera patients who responded to Vorinostat indicating that YKL-40 might  be a novel marker for disease burden.

In conclusion, this trial showed that Vorinostat was effective in normalising blood counts and resolving pruritus (itching) in patients with polycythaemia vera and essential thrombocythaemia. However, at the dose given the rate of discontinuation of the drug was high due to significant side effects and perhaps a lower dose should be considered in the future. 

Of note, two patients found the therapy the only acceptable one for control of their disease and remain on therapy.

Publications from the funding provided by MPN Voice are highlighted below.

A phase II study of Vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia.
Br. J. Haematol. (2013) Aug; 162(4) 498-508. PMID: 23758082.


Circulating YKL-40 in patients with essential thrombocythaemia and polycythemia vera treated with the novel histone deacetylase inhibitor Vorinostat.
Leukemia Research (2014) 38(7): 816-21. PMID: 24836761